Optical coherence tomography (OCT) is a high-resolution medical and biological imaging technology. OCT utilizes low-coherence interferometry (LCI) to perform optical ranging within biological tissues. OCT has already previously been demonstrated for being a high resolution real time imaging modality that can provide near-histological information in other clinical applications such as ophthalmology, cardiology, and digestive disease. In use, OCT detects the reflections of low-coherence light, and cross-sectional imaging may be performed by measuring the backscattered intensity of light from structures in tissue. This imaging technique is attractive for medical imaging because it permits the imaging of tissue microstructure in situ. In situ imaging with OCT provides micron-scale imaging resolution without the need for excision and histological processing. OCT has been used in ophthalmology for high-resolution tomographic imaging of the retina and anterior eye. Recently, the technique has been applied for imaging a wide range of nontransparent tissues to investigate applications in tissues studies and medical applications in gastroenterology, urology, and neurosurgery.
OCT measures cross-sectional tomographic images in tissue and is similar to ultrasound B-mode imaging except that it uses light waves rather than sound. OCT also differs from ultrasound in that the detection in OCT is based on interferometry. In ultrasound, the time the ultrasound pulse takes to travel to a surface and be reflected back can be measured by an electronic clock. However, this is not possible with optical techniques because of the high speeds associated with the propagation of light. This limitation is overcome with the use of a reference light path and interferometry. A detailed presentation of the principles of operation of OCT and factors that govern its performance have been previously published. (See Huang D, Swanson, Lin C P, Schuman J S, Stinson W G, Chang W, Hee M R, Flotte T, Gregory K, Puliafito C A, Fujimot J G. Optical coherence tomography. Science. 1991:254:1178-1181; and Swanson E A, Izatt J, Hee M R, Huang D, Lin C P, Schuman J S, Puliafito C A, Fujimoto J G. In vivo retinal imaging by optical coherence tomography. Optics Lett. 1993; 18:1864-1866; both of which are herein incorporated by reference.)
OCT systems may use fiber optics and a compact diode light source similar to those used in compact disc players. Precision distance measurements may be performed by Michelson-type interferometry. In this case, light from the source is split by an optical fiber splitter, which functions as an interferometer. One of the fibers directs light to the tissue and the other to a moving reference mirror, in the case of time-domain OCT. The distal end of the optical fiber can be interfaced to a catheter. In time-domain OCT, the position of the reference mirror is precisely controlled by the system electronics. The light signal reflected from the tissue is recombined with the signal reflected from the mirror. Interference between the light reflected from the tissue and the light reflected from the reference mirror occurs only when the two path lengths are matched to within the coherence length of the light source. This allows precise (micron scale) determination of the distance within the sample from which the light was reflected.
OCT therefore measures the intensity of backscattered (reflected) light from within the tissue, plotted as a function of depth. A cross-sectional image is produced in a manner similar to radar by recording axial reflectance profiles while the transverse position of the optical beam on the tissue specimen is scanned. The image is displayed either in gray scale or false color in order to differentiate tissue microstructure.
Spectroscopic optical coherence tomography (SOCT) is an extension of OCT that can differentiate between different types of tissue. In addition to the normal OCT measurement of the intensity of light backscattered from the sample, SOCT measures the spectral absorption and scattering data from the tissue. Tissue structure can be resolved based on local optical densities, ignoring the frequency dependent changes. SOCT resolves both the amplitude, which contains the scattering and refractive of index information, and the frequency, which contains spectroscopic molecular composition information based on the absorption and scattering properties.
Contrast agents may be used to improve the specificity and targeted tissue visualization of images obtained from an imaging technique, including OCT. Conventional contrast agents serve to increase the intensity of backscattered light. For example, air-filled micro-bubbles and engineering microspheres may be introduced into tissue to increase the backscattering from tissue. In another example, a molecular contrast agent can be used in a pump-probe technique to change the absorption properties of the light.
Otoscopy based on pneumatic otoscopes is currently the primary diagnostic tool for ear pathologies, and virtually every physician in internal medicine, pediatrics, or family practice medicine. However, the diagnostic process is currently more subjective than objective, more of an art than a science. Trained eyes are required to decipher a wide variety of tympanic membrane and middle-ear images and findings, some of which are empirically linked to various disease states. The treatments that follow rely on the individual judgments of physicians.
Currently, few objective tests are available to assess the significance of the pathology of the ear, and limitations are more evident in the primary care or general pediatricians' office, remote from access to specialists in otolaryngology. Furthermore, evaluation and monitoring of treatments (such as antibiotic treatments in otitis media (OM) or otitis media with effusion (OME)) in patients is often difficult, because quantitative measures are lacking. All of these limitations can be ultimately attributed to the qualitative nature of the information acquired, because a pneumatic otoscope is basically a low-magnification microscopy-type instrument.
Other than pneumatic otoscopy, there are mainly two additional in vivo diagnostic methods for identifying middle-ear pathologies: tympanometry and acoustic reflectometry. Tympanometry measures sound energy transmission/reflection (i.e., compliance/mobility) of the tympanic membrane by recording a tympanogram in response to air pressure changes inside the ear canal. Tympanograms are classified as type A (normal), type B (indicating middle-ear effusion) or type C (indicating eustachian tube dysfunction). Acoustic reflectometry measures the acoustic reflectivity spectrum of the middle-ear in response to an incident sound. The curve of the spectrum is used to characterize the extent of OME.
Comprehensive evidence assessment on the accuracy (sensitivity and specificity) of the three methods reveals that pneumatic otoscopy has better performance than the two acoustic methods. Furthermore, pneumatic otoscopy is more cost-effective and easier to use. Thus, a 2004 clinical practice guideline on OME from the American Academy of Pediatrics has recommended that clinicians use pneumatic otoscopy as the primary diagnostic method (See American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck Surgery, and American Academy of Pediatrics Subcommittee on Otitis Media With Effusion, “Otitis Media With Effusion,” Pediatrics, 113, 1412-1429, 2004). However, none of the three described established methods are able to assess or monitor the presence of biofilms within the middle ear.
Biofilms are microorganisms that grow collectively in adhesive polymers (mainly extracellular polysaccharides (EPS)) on biologic or non-biologic surfaces. Biofilms can virtually colonize any indwelling device (catheters, artificial joints, contact lenses) and different tissues (oral soft tissues, teeth, middle ear, gastrointestinal tract, urogenital tract, airway/lung tissue, etc.) (Costerton J W, Stewart P S, Greenberg E P (1999) Bacterial biofilms: a common cause of persistent infections. Science 284, 1318-1322; Donlan R M (2001) Biofilms and device-associated infections. Emerg Infect Dis 7, 277-281; Donlan R M (2002) Biofilms: microbial life on surfaces. Emerg Infect Dis 8, 881-890; Fux C A, Costerton J W, Stewart P S, Stoodley P (2005) Survival strategies of infectious biofilms. Trends Microbiol 13, 34-40). Bacteria embedded in biofilms is very difficult to be eradicated. Biofilms colonized on devices are the sources of most medical device-related infections. Bacterial biofilms are found colonizing the middle ear in most patients with chronic otitis media and may be the cause of recurrent otitis media (L. Hall-Stoodley, F. Z. Hu; A. Gieseke, L. Nistico, D, Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA. 296, 202-211, 2006).
In one publication, the use of OCT for imaging the middle ear structures has been studied, primarily for assessing feasibility for imaging the ossicles within the middle ear (See C. Pitris, K. T. Saunders, J. G. Fujimoto, M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch Otolaryngol Head Neck Surg. 127, 637-642, 2001.) This study was conducted on cadaver tissue. Other optical imaging efforts have focused on imaging the round window within the middle ear, but this requires surgical intervention for access. A recent study in JAMA (See L. Hall-Stoodley, F. Z. Hu; A. Gieseke, L. Nistico, D, Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA. 296, 202-211, 2006.), documented the evidence of biofilms being linked to chronic OM, and used invasive tissue sampling followed by confocal microscopy for identifying biofilms. However, all of these methods were invasive and required getting a tissue sample. There is a need for non-invasive detection of biofilms in the inner ear or analysis of effusion composition in OME.